Effects of Matuzumab in Combination With Pemetrexed for the Treatment of Advanced Lung Cancer

• Overall Survival [ Time Frame: various timepoints measred ] [ Designated as safety issue: No ]
• Time to tumor progression [ Time Frame: various timepoints measured ] [ Designated as safety issue: No ]
• Duration of response [ Time Frame: various timepoints measured ] [ Designated as safety issue: No ]
• Safety and tolerability [ Time Frame: various timepoints measured ] [ Designated as safety issue: No ]
• Quality of life [ Time Frame: various timepoints measured ] [ Designated as safety issue: No ]

This study is planned to answer questions about how the drug, matuzumab (EMD 72000), works and is part of an effort aimed to develop better treatment for advanced lung cancer by combining matuzumab, a monoclonal antibody, with a chemotherapy treatment, called pemetrexed. Pemetrexed is commercially available and has been approved for treatment of locally advanced or metastatic non-small cell lung cancer that could not be successfully treated with other chemotherapy.

The study aims to examine how non-small cell lung cancer (NSCLC) responds to matuzumab in combination with pemetrexed, as compared with giving pemetrexed alone. The study also aims to examine how safe and effective matuzumab is and for how long it stays in the body (pharmacokinetics). Matuzumab is an experimental treatment which is currently only available for research studies.

• Lung Cancer
• Non Small Cell Lung Carcinoma

• Drug: Pemetrexed
  pemetrexed 500mg per metre squared given i.v. (into the vein) every 3 weeks until progression of disease or unacceptable toxicity
• Drug: Matuzumab + Pemetrexed
  matuzumab 800mg given i.v. every week plus pemetrexed as in Group 1 until progression of disease or unacceptable toxicity
• Drug: Matuzumab + Pemetrexed
  matuzumab 1600mg given i.v. every 3 weeks plus pemetrexed as in Group 1 until progression of disease or unacceptable toxicity

• Active Comparator: 1
  Intervention: Drug: Pemetrexed
• Experimental: 2
  Intervention: Drug: Matuzumab + Pemetrexed
• Experimental: 3
  Intervention: Drug: Matuzumab + Pemetrexed

Inclusion Criteria:

• Written informed consent provided prior to any screening procedure
• Male or female,> 18 years of age
• Histologically or cytologically confirmed diagnosis of non-small cell lung cancer
• Demonstrated progressive disease on or after first-line chemotherapy for stage IIIB/IV disease. The first-line therapy must consist of platinum-based regimens in combination with taxanes,gemcitabine or vinorelbine.. Stage IIIB/IV patients must have measurable disease (tumor) without clinically significant pleural unless the pleural effusion can be effectively drained prior to admission into the study.
• A chemotherapy-free interval of at least 3 weeks between the end of first-line chemotherapy and start of study treatment
• At least 1 measurable lesion according to the modified WHO criteria
• Archived tissue or cytologic sample available for the determination of EGFR expression
• ECOG performance status 0-1
• Life expectancy >12 weeks
• Adequate baseline organ functions, defined as follows: *Serum creatinine ≤1.5 × upper limit of normal (ULN). In case of borderline values for serum creatinine, creatinine clearance must be ≥45 mL/min; *Total bilirubin <1.5 × ULN; *Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) ≤2.5 × ULN (Subjects with liver metastases should have ALT/AST <5 × ULN.); *Absolute neutrophil count ≥1500/mm3; *Platelet count ≥100,000/mm3; *Hemoglobin level ≥10 g/dL11
• If procreative potential (male or female), willingness to use effective contraceptive methods for the duration of treatment and continuing for 2 months after the last dose. Subjects of procreative potential are defined as any fertile male, or any female who has experienced menarche and who is not postmenopausal (defined as age-related amenorrhea ≥12 months) or who has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy)

Exclusion Criteria:

• Radiotherapy or major surgery within 30 days prior to the start of study treatment
• Prior treatment with an EGFR-directed therapy or with EGFR signal transduction inhibitors
• Prior treatment with pemetrexed
• Pregnant (confirmed by β-HCG) or lactating female
• Weight loss >10% within 12 weeks prior to the start of study treatment
• Documented or symptomatic brain metastases or leptomeningeal disease
• Myocardial infarction within 6 months prior to the start of study treatment, uncontrolled congestive heart failure, or any current New York Heart Association Grade III or IV cardiovascular disorder despite treatment
• Presence of a ≥Grade 2 preexisting skin disorder (except for alopecia)
• Previous diagnosis of autoimmune disease with significant organ involvement
• Concurrent malignancies or invasive carcinomas diagnosed within the past 5 years, except for adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix
• Any significant disease that, in the Investigator's opinion, should exclude the subject from the study
• History of significant neurologic or psychiatric disorder (e.g., dementia, seizures, or bipolar disorder)
• History of drug abuse within 6 months prior to the start of study treatment
• Known conditions that require concurrent treatment with a nonpermitted drug
• Presence of a contraindication to the study treatment(s) according to the current Investigator's Brochure (IB) for matuzumab and the labeling for pemetrexed
• Known hypersensitivity to the study treatment or any of its components
• Participation in another clinical study within 30 days prior to the start of study treatment